2-cyano-4-fluoropyrrolidine derivative or its salt

Abstract

Provided is a compound having excellent dipeptidyl peptidase IV-inhibiting activity, and a remedy based on the activity for insulin-dependent diabetes (type 1 diabetes), especially for non insulin-dependent diabetes (type 2 diabetes), insulin-resistant disorders, and obesity.

1. A 2-cyano-4-fluoropyrrolidine compound of Formula (I): 
       
         
           
           
               
               
           
         
         wherein A is a group of Formula (II): 
       
       
         
           
           
               
               
           
         
         wherein R 1 -B represents methanesulfonyl, formyl or acetyl which may be substituted by a group selected from the group consisting of —OH and fluoro; 
         R 2  represents —H, methyl or ethyl; 
       
       or a pharmaceutically acceptable salt thereof. 
     
     
       2. A compound selected from the group consisting of:
 4-fluoro-1-({[1-(methanesulfonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile, 
 4-fluoro-1-({[4-methyl-1-(methanesulfonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile, 
 4-fluoro-1-{[(1-glycoloylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile, 
 4-fluoro-1-{[(1-glycoloyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile 
 4-fluoro-1-{[(1-fluoroacetyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine -2-carbonitrile, 
 4-fluoro-1-{[(1-formylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile, 
 4-fluoro-1-{[(1-formyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile, and 
 4-fluoro-1-({[1-(morpholin-4-ylcarbonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile, 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
       3. A pharmaceutical composition comprising an effective amount of the compound or pharmaceutical acceptable salt thereof of  claim 1  as an active ingredient, and a pharmaceutically acceptable carrier. 
     
     
       4. The compound according to  claim 1 , wherein the compound is selected from the group consisting of:
 (2S,4S)-4-fluoro-1-({[4-methyl-1-(methanesulfonyl)piperidin-4-yl]amino}acetyl)pyrrolidine-2-carbonitrile, 
 (2S,4S)-4-fluoro-1-{[(1-glycoloyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile, 
 (2S,4S)-4-fluoro-1-{[(1-fluoroacetyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile, and 
 (2S,4S)-4-fluoro-1-{[(1-formyl-4-methylpiperidin-4-yl)amino]acetyl}pyrrolidine-2-carbonitrile, 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
       5. A pharmaceutical composition comprising an effective amount of the compound or pharmaceutical acceptable salt thereof of  claim 4  as an active ingredient, and a pharmaceutically acceptable carrier.